Caprylyl Glycol (CAS #1117-86-6) GreenScreen for Safer...

Template Copyright 2014 © Clean Production Action

Content Copyright 2016 © ToxServices

GreenScreen® Version 1.2 Reporting Template – October 2014 GS-592

Limited license provided to EDF for posting via EDF’s website at https://www.edf.org/. Further copying, resale,

and distribution are expressly prohibited.

Caprylyl Glycol (CAS #1117-86-6) GreenScreen® for Safer Chemicals (GreenScreen®)

Assessment

Prepared for:

Environmental Defense Fund

February 1, 2016

1367 Connecticut Ave., N.W., Suite 300

Washington, D.C. 20036

https://www.edf.org/






TABLE OF CONTENTS

GreenScreen® Executive Summary for Caprylyl Glycol (CAS 1117-86-6) ............................................... 1

Chemical Name ........................................................................................................................................... 1

GreenScreen® Summary Rating for ............................................................................................................ 3

Transformation Products and Ratings ......................................................................................................... 4

Introduction ................................................................................................................................................. 4

PhysicoChemical Properties of Caprylyl Glycol ........................................................................................ 6

Group I Human Health Effects (Group I Human) ...................................................................................... 6

Carcinogenicity (C) Score ....................................................................................................................... 6

Mutagenicity/Genotoxicity (M) Score .................................................................................................... 7

Reproductive Toxicity (R) Score ............................................................................................................. 9

Developmental Toxicity incl. Developmental Neurotoxicity (D) Score ............................................... 10

Endocrine Activity (E) Score ................................................................................................................ 11

Group II and II* Human Health Effects (Group II and II* Human) ......................................................... 11

Acute Mammalian Toxicity (AT) Group II Score ................................................................................. 12

Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST) ............................................................... 12

Group II Score (single dose) .............................................................................................................. 12

Group II* Score (repeated dose) ........................................................................................................ 13

Neurotoxicity (N) .................................................................................................................................. 15

Group II Score (single dose) .............................................................................................................. 15

Group II* Score (repeated dose) ........................................................................................................ 16

Skin Sensitization (SnS) Group II* Score ............................................................................................. 17

Respiratory Sensitization (SnR) Group II* Score ................................................................................. 18

Skin Irritation/Corrosivity (IrS) Group II Score .................................................................................... 18

Eye Irritation/Corrosivity (IrE) Group II Score ..................................................................................... 19

Ecotoxicity (Ecotox) ................................................................................................................................. 21

Acute Aquatic Toxicity (AA) Score ...................................................................................................... 21

Chronic Aquatic Toxicity (CA) Score ................................................................................................... 21

Environmental Fate (Fate) ........................................................................................................................ 21

Persistence (P) Score ............................................................................................................................. 21

Bioaccumulation (B) Score ................................................................................................................... 22

Physical Hazards (Physical) ...................................................................................................................... 23

Reactivity (Rx) Score ............................................................................................................................ 23

Flammability (F) Score.......................................................................................................................... 23

References ................................................................................................................................................. 24

APPENDIX A: Hazard Benchmark Acronyms ........................................................................................ 27

APPENDIX B: Results of Automated GreenScreen® Score Calculation for Caprylyl Glycol

(CAS# 1117-86-6) .............................................................................................................................. 28

APPENDIX C: Pharos Output for Caprylyl Glycol (CAS# 1117-86-6) .................................................. 29







APPENDIX D: Toxtree Carcinogenicity Results for Caprylyl Glycol (CAS# 1117-86-6) ...................... 30

APPENDIX E: VEGA Carcinogenicity Results for Caprylyl Glycol (CAS# 1117-86-6) ....................... 31

APPENDIX F: ECOSAR Modeling Results for Caprylyl Glycol (CAS# 1117-86-6) ............................. 34

APPENDIX J: EPISuite Modeling Results for Caprylyl Glycol (CAS# 1117-86-6) ............................... 36

Licensed GreenScreen® Profilers .............................................................................................................. 39

TABLE OF FIGURES

Figure 1: GreenScreen® Hazard Ratings for Caprylyl Glycol .................................................................... 3

TABLE OF TABLES

Table 1: Physical and Chemical Properties of Caprylyl Glycol (CAS #1117-86-6) .................................. 6




and distribution are expressly prohibited. Page i

GreenScreen® Executive Summary for Caprylyl Glycol (CAS 1117-86-6)

Caprylyl glycol is used primarily in cosmetic formulations as a preservative, a skin and hair

conditioning agent, and a viscosity agent.

Caprylyl glycol was assigned a GreenScreen BenchmarkTM Score of 3 (“Use but Still Opportunity

for Improvement”). This score is based on the following hazard score combinations:

Benchmark 3b

o High Ecotoxicity (acute aquatic toxicity (AA))

o Moderate Ecotoxicity (chronic aquatic toxicity (CA))

Benchmark 3c

o High Group II Human Toxicity (eye irritation (IrE))

o Moderate Group II Human Toxicity (single dose systemic toxicity (STs))

Data gaps (DG) exist for endocrine activity (E) and respiratory sensitization (SnR*). As outlined in

CPA (2013) Section 12.2 (Step 8 – Conduct a Data Gap Analysis to assign a final Benchmark score),

caprylyl glycol meets requirements for a GreenScreen® Benchmark Score of 3 despite the hazard

data gaps. In a worst-case scenario, if caprylyl glycol were assigned a High score for the data gap E,

it would be categorized as a Benchmark 1 Chemical.

GreenScreen® Benchmark Score for Relevant Route of Exposure:

As a standard approach for GreenScreen® evaluations, all exposure routes (oral, dermal, and

inhalation) were evaluated together, so the GreenScreen® Benchmark Score of 3 (“Use but Still

Opportunity for Improvement”) is applicable for all routes of exposure.

GreenScreen® Hazard Ratings for Caprylyl Glycol (CAS 1117-86-6)

C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F

single repeated* single repeated*

L L L L DG L DG L M L L DG L H H M vL vL L L

Fate Physical

ST N

Group I Human Group II and II* Human Ecotox

Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated

values, authoritative B lists, screening lists, weak analogues, and lower confidence. Hazard levels in BOLD font are

used with good quality data, authoritative A lists, or strong analogues. Group II Human Health endpoints differ

from Group II* Human Health endpoints in that they have four hazard scores (i.e., vH, H, M, and L) instead of three

(i.e., H, M, and L), and are based on single exposures instead of repeated exposures. Please see Appendix A for a

glossary of hazard acronyms. DG: Data Gap




and distribution are expressly prohibited. Page 1 of 39

GreenScreen® Assessment for Caprylyl Glycol (CAS# 1117-86-6)

Method Version: GreenScreen® Version 1.21

Assessment Type2: Certified

Chemical Name: Caprylyl glycol

CAS Number: 1117-86-6

GreenScreen® Assessment Prepared By:

Quality Control Performed By:

Name: Mouna Zachary, Ph.D. Name: Bingxuan Wang, Ph.D., D.A.B.T.

Title: Toxicologist Title: Toxicologist

Organization: ToxServices LLC Organization: ToxServices LLC

Date: March 27, 2015, November 30, 2015 Date: April 7, 2015, Dec 14, 2015, Feb 1, 2016

Assessor Type: Licensed GreenScreen® Profiler Assessor Type: Licensed GreenScreen® Profiler

Confirm application of the de minimus rule3: According to some specification sheets, caprylyl

glycol can contain heavy metal impurities of up to 5 ppm (CIR 2011). This assessment was

conducted for the theoretically pure substance.

Chemical Structure(s):

Caprylyl glycol (CAS # 1117-86-6)

Also called:

1,2-Dihydroxyoctane; 1,2-octylene glycol; octane-1,2-diol; 1,2-octanediol (ChemIDplus 2015)

Chemical Structure(s) of Chemical Surrogates Used in the GreenScreen®:

In the absence of available data for the chemical of interest, ToxServices searched for a suitable

analog or class of analogs using guidance in the U.S. EPA’s procedure for identifying analogs (U.S.

EPA 2010), ECHA’s read across assessment framework (ECHA 2015a) and OECD’s guidance on

grouping of chemicals (OECD 2014). Resources used for the surrogate search included the

1 Use GreenScreen® Assessment Procedure (Guidance) V1.2 2 GreenScreen® reports are either “UNACCREDITED” (by unaccredited person), “AUTHORIZED” (by Authorized

GreenScreen® Practitioner), “CERTIFIED” (by Licensed GreenScreen® Profiler or equivalent) or “CERTIFIED WITH

VERIFICATION” (Certified or Authorized assessment that has passed GreenScreen® Verification Program) 3 Every chemical in a material or formulation should be assessed if it is:

1. intentionally added and/or

2. present at greater than or equal to 100 ppm

Name: Jennifer Rutkiewicz, Ph.D.

Title: Toxicologist

Organization: ToxServices LLC

Update Date: December 4, 2015

Assessor Type: Licensed GreenScreen® Profiler





ChemIDplus structural similarity search, OECD Toolbox, U.S. EPA’s Analog Identification

Methodology (AIM), and U.S. EPA’s Chemical Assessment Clustering Engine (ChemACE).

Surrogates were considered to be appropriate if they resemble the target in terms of molecular

structure and size, contain a substructure of functional group that may play a critical toxicological

role, share similar physicochemical properties (e.g. water solubility, partition coefficient), or have

common or similar precursors, metabolites, or breakdown products. Where surrogates are used to fill

data gaps or as supporting evidence, the use of a surrogate is clearly indicated for that endpoint.

Caprylyl glycol has a relatively complete toxicological dataset. The Cosmetics Ingredient Review

(CIR) Expert Panel reviewed a number of 1,2 glycol compounds, including caprylyl glycol in a group

as these chemicals have similar structures and physicochemical properties, and therefore are expected

to have similar toxicities (CIR 2011). Each of these compounds has a hydroxyl group (-OH) on the

first and second carbons and varies only by the number of carbons. ToxServices used data on other

members of this group when no data are available for caprylyl glycol. Consistent results among the

class members indicate a similar order of toxicity for the glycol class members and support the use of

the surrogates to approximate the toxicity of caprylyl glycol. Although the alkyl chain is not expected

to contribute to toxicity, physicochemical properties and bioavailability may differ slightly between

caprylyl glycol and the surrogates with much shorter or longer alkyl chain lengths. The surrogates

with carbon numbers ranging from 6-10 were considered to be the strongest surrogates as they are

most similar in size to caprylyl glycol. When scores were based entirely on data for glycols with

carbon numbers less than 6, the confidence level was reduced.

Propylene glycol (CAS# 57-55-6)

Butane-1,2-diol (CAS# 584-03-2)

Hexane-1,2-diol (CAS# 6920-22-5)

Decane-1,2-diol(CAS# 1119-86-4)





Pentane-1,2-diol (CAS# 5343-92-0)

Identify Applications/Functional Uses: (CIR 2011)

1. As an emollient, humectant, and hair and skin conditioning agent in personal care product

formulations at 0.00003 – 5%.

2. As a preservative (at 0.00003 – 5% in personal care products)

GreenScreen® Summary Rating for Capryly Glycol4: Caprylyl glycol was assigned a

GreenScreen BenchmarkTM Score of 3 (“Use but Still Opportunity for Improvement”) (CPA 2014).

This score is based on the following hazard score combinations:

Benchmark 3b

o High Ecotoxicity (acute aquatic toxicity (AA))

o Moderate Ecotoxicity (chronic aquatic toxicity (CA))

Benchmark 3c

o High Group II Human Toxicity (eye irritation (IrE))

o Moderate Group II Human Toxicity (single dose systemic toxicity (STs))

Data gaps (DG) exist for endocrine activity (E) and respiratory sensitization (SnR*). As outlined in

CPA (2013) Section 12.2 (Step 8 – Conduct a Data Gap Analysis to assign a final Benchmark score),

caprylyl glycol meets requirements for a GreenScreen® Benchmark Score of 3 despite the hazard

data gaps. In a worst-case scenario, if caprylyl glycol were assigned a High score for the data gap E,

it would be categorized as a Benchmark 1 Chemical.

Figure 1: GreenScreen® Hazard Ratings for Caprylyl Glycol

C M R D E AT SnS* SnR* IrS IrE AA CA P B Rx F

single repeated* single repeated*

L L L L DG L DG L M L L DG L H H M vL vL L L

Fate Physical

ST N

Group I Human Group II and II* Human Ecotox

Note: Hazard levels (Very High (vH), High (H), Moderate (M), Low (L), Very Low (vL)) in italics reflect estimated

(modeled) values, authoritative B lists, screening lists, weak analogues and lower confidence. Hazard levels in

BOLD font are used with good quality data, authoritative A lists, or strong analogues. Group II Human Health

endpoints differ from Group II* Human Health endpoints in that they have four hazard scores (i.e. vH, H, M, and L)

instead of three (i.e. H, M, and L), and are based on single exposures instead of repeated exposures. Please see

Appendix A for a glossary of hazard acronyms. DG: Data Gap

4 For inorganic chemicals with low human and ecotoxicity across all hazard endpoints and low bioaccumulation potential,

persistence alone will not be deemed problematic. Inorganic chemicals that are only persistent will be evaluated under the

criteria for Benchmark 4.





Transformation Products and Ratings:

Identify feasible and relevant fate and transformation products (i.e., dissociation products,

transformation products, valence states) and/or moieties of concern5

No transformation products were identified for caprylyl glycol. Based on available data on its

surrogate, propylene glycol, it is not susceptible to hydrolysis due to lack of functional groups that

hydrolyze under environmental conditions. In addition, volatility is expected to be negligible due to

its low vapor pressure. Based on its molecular formula, possible combustion products of caprylyl

glycol are CO and CO2, which are naturally occurring, ambient substances and not relevant with

respect to the GreenScreen® Benchmark score for caprylyl glycol.

Introduction

Caprylyl glycol, also called 1,2-octanediol, belongs to the chemical class of 1,2 glycols. Each of

these compounds has a hydroxyl group (-OH) on the first and second carbons and varies only by the

number of carbons. These compounds are produced commercially by either catalytic oxidation of

alkene oxides, or reduction of 2-hydroxy acids (CIR 2011).

Caprylyl glycol is used as a skin and hair conditioning agent, a viscosity agent in cosmetic products,

and has also been used as an alternative to paraben preservatives (CIR 2012, 2014). The CIR Expert

Panel concluded that caprylyl glycol is safe for use in cosmetics in the present practices of use and

concentration evaluated by the panel (0.0003 to 5% for dermal contact cosmetics). The CIR Expert

Panel noted the potential for caprylyl glycol, decylene glycol, pentylene glycol, 1,2-butanediol, and

1,2-hexanediol to be skin penetration enhancers. The CIR recommended that if caprylyl glycol is

used in a formulation that contains ingredients whose safety is concluded based on the lack of dermal

penetration of such ingredients, then industry is advised to consider the impact of the penetration

enhancing activity of these ingredients on the safety of other ingredients in formulation (CIR 2012).

Caprylyl glycol is not listed as a prohibited ingredient in Annex II of EC Regulation No. 1223/2009

(EU 2009). Caprylyl glycol can also function as a cosmetic preservative as an alternative to parabens

(CIR 2012). However, it is not an approved cosmetic preservative in the EU because it is not

included as such on Annex V of EC Regulation No. 1223/2009 (EU 2009).

ToxServices assessed caprylyl glycol against GreenScreen® Version 1.2 (CPA 2013) following

procedures outlined in ToxServices’ SOP 1.69 (GreenScreen® Hazard Assessment) (ToxServices

2013).

Preservative Spectrum of Effect:

The antimicrobial activity of vicinal diols increases as chain length increases, up to caprylyl glycol

(8C); after caprylyl glycol the efficacy decreases rapidly due to limited water solubility (Varvaresou

et al. 2009). Caprylyl glycol’s emulsifier-like structure interferes with the cellular structures of

microorganisms and disintegrates cells membranes (Papageurgiou et al 2010). Specifically in

moisturizers, 1,2-glycols work by binding much of the available water, thereby reducing the water

activity of the end product beyond the point where microorganisms can survive (Godfrey 2012).

5 A moiety is a discrete chemical entity that is a constituent part or component of a substance. A moiety of concern is often the

parent substance itself for organic compounds. For inorganic compounds, the moiety of concern is typically a dissociated

component of the substance or a transformation product.





As summarized below, caprylyl glycol has a good spectrum of effect on gram-positive and gram-

negative bacteria and a moderate effect on yeast and molds. Caprylyl glycol has antimicrobial

activity against gram-positive and gram-negative bacteria, such as Staphylococcus aureus,

Pseudomonas aeruginosa and Escherichia coli, at concentrations as low as 0.5%. Caprylyl glycol

has antimicrobial activity against yeasts and molds such as Candida albicans and Aspergillus niger at

concentrations as low as 0.5%; however, it is not as effective. Additionally, caprylyl glycol is able to

improve the preservative effectiveness of other preservatives at concentrations lower than their

typical doses. These conclusions are detailed in the studies described below.

Caprylyl Glycol’s Preservative Spectrum of Effect

Microorganism Spectrum of Effect Reference

Gram-positive bacteria Good Varvaresou et al. 2009, Lawan et al. 2009,

Pillai et al. 2008

Gram-negative bacteria Good Varvaresou et al. 2009, Lawan et al. 2009,

Pillai et al. 2008

Yeasts/Molds Moderate Varvaresou et al. 2009, Lawan et al. 2009,

Pillai et al. 2008

The combination of caprylyl glycol 0.3% (w/w) with the traditional preservatives Phenonip® or

Euxyl K702® (phenoxyethanol/benzoic acid/dehydracetic acid) at approximately 50% of the

recommended use levels led to a significant improvement in antimicrobial activity. Specifically, it

contributed to inhibition of Staphylococcus aureus and Pseudomonas aeruginosa, and improved

antimicrobial activity against Escherichia coli, Candida albicans, and Aspergillus niger. Recently, it

has been reported that caprylyl glycol as a sole preservative at a concentration of 0.5-1% (w/w) is

sufficient for the preservation of a variety of O/W and aqueous formulations (Varvaresou et al.

2009).

The individual and synergistic function on antimicrobial activities of ethylhexylglycerin and caprylyl

glycol against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans,

and Aspergillus niger were evaluated at various concentrations. The minimum concentration of 0.5%

caprylyl glycol inhibited S. aureus, P. aeruginosa, E. coli, and C. albicans within 1 day, and

inhibited A. niger within 28 days. A mixture of caprylyl glycol and phenoxyethanol (1:3), had a

minimum concentration of 1.0% to inhibit P. aeruginosa, E. coli, and C. albicans within 1 day, S.

aureus within 3 days, and A. niger within 28 days (Lawan et al. 2009).

The minimum inhibitory concentration (MIC) of caprylyl glycol was tested using a standard agar

dilution method. The MICs were as follows: 1.25% for Staphylococcus aureus, 0.63% for

Pseudomonas aeruginosa, 0.63% for Escherichia coli, 0.31% for Candida albicans, and 0.16% for

Aspergillus niger. The preservative efficacy of caprylyl glycol, as well as a 1:1 blend of caprylyl

glycol with 1,2-hexanediol, and a 1:1 blend of caprylyl glycol with preservatives was determined in a

standard challenge test according to the European Pharmacoepeia. Cosmetic emulsions were

inoculated with 105 CFU/mL microorganisms and test substances for 28 days. Caprylyl glycol was

determined effective against all 5 microorganisms. A 0.5% or 1.0% w/w 1:1 blend of caprylyl glycol

and 1,2-hexanediol had excellent activity against bacteria (S. aureus, P. aeruginosa, and E. coli

eliminated by day 2) but weaker activity against yeast and molds (C. albicans eliminated by day 7, A.

niger not eliminated by 28 days). The authors found combining lower doses of preservatives that are

typically used with 1,2-alkanediols produced a robust preservative system for topical formulations

(Pillai et al. 2008).





GreenScreen® List Translator Screening Results

The GreenScreen® List Translator identifies specific authoritative or screening lists that should be

searched to identify GreenScreen® benchmark 1 chemicals (CPA 2012a). Pharos (Pharos 2015) is an

online list-searching tool that is used to screen chemicals against the List Translator electronically. It

checks all of the lists in the List Translator with the exception of the U.S. Department of

Transportation (U.S. DOT) lists (U.S. DOT 2008a,b) and these should be checked separately in

conjunction with running the Pharos query. The output indicates benchmark or possible benchmark

scores for each human health and environmental endpoint. The output for caprylyl glycol can be

found in Appendix C and a summary of the results can be found below:

Restricted List

o German FEA - Substances Hazardous to Waters - Class 2 Hazard to Waters

Caprylyl glycol is not listed by DOT.

Physicochemical Properties of Caprylyl Glycol

Caprylyl glycol is a colorless liquid that is soluble in water. Its vapor pressure of 0.28 Pa indicates

that it can form a vapor. Its measured log Kow of 2.1 indicates a low potential for bioaccumulation.

Table 1: Physical and Chemical Properties of Caprylyl Glycol (CAS #1117-86-6)

Property Value Reference

Molecular formula C8H18O2 ChemIDplus 2015

SMILES Notation C([C@@H](CO)O)CCCCC ChemIDplus 2015

Molecular weight 146.228 ChemIDplus 2015

Physical state Liquid CIR 2011, ECHA 2015b

Appearance colorless liquid CIR 2011, ECHA 2015b

Melting point 28-31°C

36 to 37°C

ECHA 2015b

CIR 2011

Vapor pressure 0.28 Pa at 25°C ECHA 2015b

Water solubility 7.5 g/L at 20°C ECHA 2015b

Dissociation constant Not identified

Density/specific gravity 0.93 g/cm³ at 20°C ECHA 2015b

Partition coefficient log Kow = 2.1 at 25°C and pH of 6 ECHA 2015b

Hazard Classification Summary Section6:

Group I Human Health Effects (Group I Human)

Carcinogenicity (C) Score (H, M, or L): L

Caprylyl glycol was assigned a score of Low for carcinogenicity based on negative findings in

animal studies for a surrogate and predicted data. GreenScreen® criteria classify chemicals as a Low

hazard for carcinogenicity when negative data, no structural alerts, and no GHS classification are

available (CPA 2012b). Confidence in the score is reduced due to the size difference between

propylene and caprylyl glycol.

Authoritative and Screening Lists

6 When original study reports were not available, ToxServices summarized study methodology, results, and study author

conclusions as reported in secondary sources. In cases where conclusions were not reported or where ToxServices interpreted the

results differently based on the information presented in the study summary, ToxServices’ conclusions are clearly stated.





o Authoritative: not listed on any authoritative lists

o Screening: not listed on any screening lists

ECHA 2015c and CIR 2011

o Oral

Surrogate: Propylene glycol: In a non-GLP compliant 2-year chronic

toxicity/carcinogenicity study, Crj: CD(SD) rats (30/sex/dose) were fed diets

containing 0, 6,250, 12,500, 25,000, and 50,000 ppm propylene glycol

(equivalent to 0, 200, 400, 900, and 1,700 mg/kg/day in males and to 0, 300, 500,

1,000, and 2,100 mg/k/day in females, as calculated by the authors of its ECHA

dossier). No evidence of any treatment-related tumors was reported under the test

conditions.

o Dermal

Surrogate: Propylene glycol: In a carcinogenicity study that predated GLP and

OECD guidelines, 50 female Swiss mice received 0.02 ml of propylene glycol

(neat, 50% and 10% solution in acetone) dermally twice a week. The animals

were observed through their life span and tumor incidence was compared with

that in a non-treated control group. No evidence of any treatment-related tumors

was reported under the test conditions.

Toxtree 2014

o Modeling was performed using Toxtree program v2.6.6. Caprylyl glycol is predicted to

be negative for both genotoxic and non-genotoxic carcinogenicity (see Appendix D).

VEGA 2012

o Caprylyl glycol is predicted to be non-carcinogenic with acceptable reliability as the

compound is in the model applicability domain (See Appendix E).

Based on the weight of evidence a score of Low was assigned. The surrogate propylene glycol

was negative in oral studies in rats and mice. In the absence of data on the target compound or a

surrogate similar in size, modeling was also performed to provide supporting data. Negative

modeling predictions also support a Low.

Mutagenicity/Genotoxicity (M) Score (H, M, or L): L

Caprylyl glycol was assigned a score of Low for mutagenicity/genotoxicity based on negative in

vitro and in vivo mutagenicity tests. GreenScreen® criteria classify chemicals as a Low hazard for

mutagenicity/genotoxicity when negative data for mutagenicity and clastogenicity, no structural

alerts, and no GHS classification are available (CPA 2012b). Confidence in the score is high because

it is based on experimental data from several well conducted and reported studies.




ECHA 2015b

o In vitro – Negative results for mutagenicity were obtained in a GLP-compliant

mammalian cell mutation assay conducted according to OECD 476 guideline. Chinese

hamster lung fibroblasts (V79) cells were exposed to caprylyl glycol (purity not

specified) in dimethyl sulphoxide (DMSO) at concentrations up to 1,480 µg/ml, with and

without metabolic activation. The first experiment involved a 4-h treatment period

whereas the second experiment involved a 24-h treatment period. No increase in the

mutation frequency was observed in the presence or absence of metabolic activation in

either experiment.





o In vitro – Negative results for mutagenicity were obtained in two GLP-compliant

bacterial reverse mutation assays conducted according to OECD 471 guideline.

Salmonella typhimurium tester strains TA 1535, TA 1537, TA 98, and TA 100, and E.

coli WP2 uvr A were exposed to caprylyl glycol (purity not specified) in DMSO at

concentrations up to 5,000 µg/plate, with and without metabolic activation. No increase

in the mutation frequency was observed in the presence or absence of metabolic

activation.

o In vitro – Negative results for clastogenicity were obtained in chromosomal aberration

test similar to OECD 473 guideline. Chinese hamster lung (CHL/IU) cell lines were

exposed to caprylyl glycol (purity not specified) in DMSO at concentration up to 700

ug/ml, with and without metabolic activation. The first experiment involved a 6-h

treatment period and concentrations up to 700 μg/ml, whereas the second experiment

involved a 24-h treatment period and concentrations up to 180 μg/ml, both with and

without metabolic activation. No increase in the frequency of chromosome aberrations

was observed with treatment in the presence or absence of metabolic activation.

CIR 2011

o In vitro – Negative results for mutagenicity were obtained in a gene mutation assay

conducted according to OECD and European Commission guidelines. Chinese

hamster V79 cells to caprylyl glycol (Dermosoft® Octiol, >98% purity) at concentrations

up to 1,480 μg/ml with and without metabolic activation. No increase in the mutation

frequency was observed in the presence or absence of metabolic activation.

UNEP 2001, ECHA 2015c (only in vivo studies on the surrogate propylene glycol are described

below, as adequate in vitro data were available for caprylyl glycol)

o Surrogate: Propylene glycol: In a pre-GLP in vivo chromosome aberration assay, male

Sprague-Dawley rats were administered 0, 30, 2,500, and 5,000 mg/kg propylene glycol

(purity not reported) by oral gavage either once or on five consecutive days. Animals

were sacrificed at 6, 24, or 48 hours following treatment and bone marrow cells were

collected. . Occasional statistically significant differences were reported in the mid and

high-dose groups (no further details provided). However, when these differences were

compared with historic data, they were considered by the study authors as consequence of

unrepresentative control data rather than a substance specific effect (no additional details

were provided). Based on this, the study authors concluded that propylene glycol had no

capacity to induce heritable mutations in the male rat.

o Surrogate: Propylene glycol: An in vivo mouse micronucleus study was negative for

clastogenicity. Male mice (n=6) were given a single intraperitoneal injection of

propylene glycol (purity 99%) in saline at concentrations of 0, 2,500, 5,000, 10,000, or

15,000 mg/kg. Animals were euthanized 18 hours after exposure and bone marrow cells

were collected. There were no increases in micronucleated polychromatic erythrocytes

seen at any dose levels. o Surrogate: Propylene glycol: An in vivo dominant lethal assay was negative for

clastogenicity. Male and female rats were administered by gavage propylene glycol at

dose levels of 30, 2,500, or 5,000 mg/kg propylene glycol (purity not reported) either

once (acute study) or for 5 days (1 dose/day, subacute study). Following the treatment,

the males were sequentially mated to 2 females per week for 8 weeks (7 weeks in

subacute study). Females were killed 14 days after separating from the males, and at

necropsy the uterus was examined for early deaths, late fetal deaths and total

implantations. There were no increases in dominant lethal (heritable) mutations in male

rats at any dose levels.





Based on the weight of evidence, a score of Low was assigned. Bacterial and mammalian cell

mutagenicity assays and a chromosome aberration assay were negative for caprylyl glycol. In

vivo data for the surrogate propylene glycol were also evaluated to support the score of Low.

Occasionally positive results, which authors attributed to unrepresentative control data, were seen

in one in vivo chromosome aberration assay in rats; historical control data could not be obtained

to confirm this conclusion. However, propylene glycol was negative for clastogenicity in in vivo

micronucleus and dominant lethal assays, and when considered in conjunction with negative

results in the in vitro assays of caprylyl glycol the weight of evidence indicates that these

compounds are not likely to be genotoxic.

Reproductive Toxicity (R) Score (H, M, or L): L

Caprylyl glycol was assigned a score of Low for reproductive toxicity based on negative results for

surrogates in animal studies. Confidence level was high because although limited relevant endpoints

are examined in OECD 421 studies, the NTP continuous breeding protocol is a comprehensive

testing protocol for reproductive toxicity testing. GreenScreen® criteria classify chemicals as a Low

hazard for reproductive toxicity when negative data for reproductive toxicity, no structural alerts, and

no GHS classification are available (CPA 2012b). Confidence in the score is reduced due to size

differences between caprylyl glycol and the surrogates.




ECHA 2015b and CIR 2011

o Surrogate: Butane-1,2-diol: In a combined repeated dose toxicity study with

reproduction/developmental toxicity screening test conducted similar to OECD Guideline

421, Sprague-Dawley rats (10/sex/dose group) were administered butane-1,2-diol (purity

not reported) in water by oral gavage at doses of 0, 40, 200, or 1,000 mg/kg/day. Male

rats were exposed for 42 days. Reproductive phase females were dosed for two weeks

prior to mating, through pregnancy, and then to postnatal day 3 (total of 45 days). The

parental animals were evaluated for clinical signs of toxicity, body weight, food

consumption, testes and epididymis weights, ovaries weight, gross pathology, and

histopathology. Hematology and blood serum chemistry were only evaluated in parental

males. Reproductive parameters (pregnancy rate, length of gestation, implantations,

corpora lutea and resorptions) were also evaluated in parental animals. No compound-

related toxicity was seen among any of the maternal groups. Slowed respiration and

decreased locomotor activity were observed in parental females at 1,000 mg/kg/day. But

these effects were all transient and mild in severity. There was no other compound-

related toxicity. There were no treatment-related effects on any of the fertility or

reproductive indices measured. The study authors identified a reproductive toxicity

NOAEL of 1,000 mg/kg/day, which was the highest dose tested.

ECHA 2015c and CIR 2011

o Surrogate: Propylene glycol: In a continuous breeding study conducted according to the

NTP protocol, male and female CD-1 mice (20/sex/group) were administered doses of 0,

1,800, 4,800, and 10,100 mg/kg propylene glycol (purity not reported) from 7 days before

mating to 98 days following mating in drinking water. Slight increases in water

consumption were observed in all parental dose groups. Body weights were unaffected.

Necropsy of F1 adults revealed no effects on mating, fertility or the number, weight, or

viability of F2 pups. The study authors reported a NOAEL of 10,100 mg/kg based on no

effects at the high dose.





Developmental Toxicity incl. Developmental Neurotoxicity (D) Score (H, M, or L): L Caprylyl glycol was assigned a score of Low for developmental toxicity based on negative findings

in well-conducted animal studies for the surrogates. GreenScreen® criteria classify chemicals as a

Low hazard for developmental toxicity when negative data for developmental toxicity, no structural

alerts, and no GHS classification are available (CPA 2012b). Confidence in the score is high because

it is based on experimental data from a well conducted study of a surrogate similar in size to caprylyl

glycol with support from data for smaller surrogates.



o Screening: not listed on any screening list

ECHA 2015b and CIR 2011

o Surrogate: Butane-1,2-diol: In the previously described repeated dose toxicity study with

reproduction/developmental toxicity screening test conducted similar to OECD Guideline

421, Sprague-Dawley rats (10/sex/dose group) were administered butane-1,2-diol (purity

not reported) in water by oral gavage at doses of 0, 40, 200, or 1,000 mg/kg/day. Male

rats were exposed for 42 days. Reproductive phase females were dosed for two weeks

prior to mating, through pregnancy, and then to postnatal day 3 (total of 45 days).

Offspring were evaluated for survival, number and sex of pups, body weight, and external

and internal abnormalities. No compound-related toxicity was seen among any of the

maternal groups. Slowed respiration and decreased locomotor activity, were observed in

parental females at 1,000 mg/kg/day. But these effects were all transient and mild in

degree. There was no other compound-related toxicity. No adverse treatment-related

fetal effects on fetal weight, litter size, or external, skeletal, or visceral malformations

were noted at any dose level. The study authors identified a developmental toxicity

NOAEL of 1,000 mg/kg/day, which was the highest dose tested.

o Surrogate: Hexane-1,2-diol: In a GLP-compliant prenatal developmental toxicity study

conducted according to OECD Guideline 414, timed pregnant female Sprague-Dawley

rats (24/dose) were administered hexane-1,2-diol in water by oral gavage at doses of 0,

30, 100, or 300 mg/kg/day hexane-1,2-diol (purity not reported) from gestation day 5 to

19. The pregnant animals were evaluated for clinical signs of toxicity, body weight, food

consumption, ovaries and uterine content, gross pathology, and histopathology.

Reproductive parameters (corpora lutea, implantation and resorptions) were also

evaluated in the treated animals. Offspring were evaluated for survival, number and sex

of pups, body weight, and external and internal abnormalities. No treatment-related

effects on clinical signs of toxicity, body weight, body weight change, food intake, or

necropsy observations were noted. There were no treatment-related effects on any of the

fertility or reproductive indices measured, either. No adverse treatment-related fetal

effects on fetal weight, litter size, or external, skeletal, or visceral malformations were

noted at any dose level. Based on this, the study authors identified a developmental and

maternal toxicity NOAEL of 300 mg/kg/day, which was the highest dose tested.

CIR 2011

o Surrogate: Propylene Glycol: A non-GLP compliant developmental toxicity study

(method not reported) was conducted using female Wistar rats (25/dose). Rats were

administered doses of 0, 16, 74.3, 345, or 1,600 mg/kg propylene glycol (purity not

reported) on days 6 to 15 of gestation via oral gavage. No effects were reported on live

litters, total or average number of implant sites, total and partial resorptions, the total and

average number of live fetuses and their sex ratio, and the number of dead fetuses or fetal





weight. Based on the available data, a NOAEL of 1,600 mg/kg was reported by the study

authors.


(method not reported) was conducted using female Dutch-belted rabbits (n=15 to 20).

Rabbits were administered doses of 0, 12.3, 57.1, 267, or 1,230 mg/kg of the test

substance (purity not reported) on days 6 to 18 of gestation via oral gavage. No effects

were reported on live litters, total or average number of implant sites, total and partial

resorptions, the total and average number of live fetuses and their sex ratio, and the

number of dead fetuses or fetal weight. Based on the available data, a NOAEL of 1,230

mg/kg was reported by the study authors.


(method not reported) was conducted using female CD-1 mice (n=25 to 28). Mice were

administered doses of 0, 16, 74.3, 345, or 1,600 mg/kg of the test substance (purity not

reported) on days 6 to 15 of gestation via oral gavage. No effects were reported on live

litters, total or average number of implant sites, total and partial resorptions, the total and

average number of live fetuses and their sex ratio, and the number of dead fetuses or fetal

weight. Based on the available data, a NOAEL of 1,600 mg/kg was reported by the study

authors.


(method not reported) was conducted using female (strain not reported) Hamsters (n=24

to 27). Hamsters were administered doses of 0, 15.5, 72.0, 334.5, or 1,550 mg/kg of the

test substance (purity not reported) on days 6 to 10 of gestation via oral gavage. No

effects were reported on live litters, total or average number of implant sites, total and

partial resorptions, the total and average number of live fetuses and their sex ratio, and

the number of dead fetuses or fetal weight. Based on the available data, a NOAEL of

1,550 mg/kg was reported by the study authors.

Endocrine Activity (E) Score (H, M, or L): DG

Caprylyl glycol was assigned a score of Data Gap for endocrine activity based on the lack of data

identified for this endpoint.




Not listed as a potential endocrine disruptor on the EU Priority List of Suspected Endocrine

Disruptors.

Not listed as a potential endocrine disruptor on the OSPAR List of Chemicals of Possible

Concern.

No data were identified for this endpoint.

Group II and II* Human Health Effects (Group II and II* Human)

Note: Group II and Group II* endpoints are distinguished in the v 1.2 Benchmark system. For

Systemic Toxicity and Neurotoxicity, Group II and II* are considered sub-endpoints and test data

for single or repeated exposures may be used. If data exist for single OR repeated exposures, then

the endpoint is not considered a data gap. If data are available for both single and repeated

exposures, then the more conservative value is used.





Acute Mammalian Toxicity (AT) Group II Score (vH, H, M, or L): L

Caprylyl glycol was assigned a score of Low for acute toxicity based on its oral LD50 value and on

inhalation and dermal acute toxicity values for the surrogates. GreenScreen® criteria classify

chemicals as a Low hazard for acute toxicity when oral and dermal LD50 values are greater than

2,000 mg/kg, inhalation LC50 values are greater than 5 mg/L (mist) and when they are not classified

to GHS (CPA 2012b). Confidence in the score is high because it is based on experimental data for

the target chemical with support from data on surrogates.

Authoritative and Screening Lists o Authoritative: not listed on any authoritative lists


ECHA 2015b

o Oral: LD50 > 2,000 mg/kg (rats)

o Inhalation:

Surrogate: Pentane-1,2-diol: LC50 > 7.015 mg/L (4hr, rats)

CIR 2011

o Dermal:

Surrogate: Decane-1,2-diol: LD50 > 2,000 mg/kg (rats)

Surrogate: Propylene Glycol: LD50 > 11,200 mg/kg (mice) and > 1,300 mg/kg

(rats)

Systemic Toxicity/Organ Effects incl. Immunotoxicity (ST)

Group II Score (single dose) (vH, H, M, or L): DG

Caprylyl glycol was assigned a score of Data Gap for systemic toxicity (single dose) based on the

lack of sufficient data.

Authoritative and Screening Lists o Authoritative: not present on any authoritative lists

o Screening: not present on any screening lists

ECHA 2015b

o Oral

In a GLP-compliant acute toxicity study conducted according to OECD 401, 5

Sprague-Dawley rats (5/sex/dose) were administered caprylyl glycol (purity not

specified) in arachis oil BP at a single dose of 2,000 mg/kg by oral gavage

followed by a 14-day observation period. No mortalities or treatment-related

effects on body weight were seen. Clinical signs of toxicity were seen in all

animals on the day of dosing and included hunched posture, lethargy, ataxia,

decreased respiratory rate and labored respiration. By two days after dosing (Day

2) all animals were entirely free from clinical signs. An oral LD50 of greater than

2,000 mg/kg was identified in this study. ToxServices identified the NOAEL at

2,000 mg/kg/day for this study based on the lack of significant systemic toxicity

observed.

o Inhalation:

Surrogate: Pentane-1,2-diol: In an acute inhalation toxicity study with a protocol

similar to the OECD 403 guideline, Tif:RAI f (SPF) rats (10/sex/dose) were

exposed by nose only inhalation to caprylyl glycol aerosol at concentrations of

3.380 or 7.015 mg/L air for 4 hours (purity not reported). Animals were then

observed for 14 consecutive days. No mortalities were observed. Clinical signs

of toxicity were seen in animals from both dose groups and included ruffled fur

and curved body position. By two days after dosing (Day 2) all animals were





entirely free from clinical signs. Macroscopic examination of each animal

revealed mottled or reddish lungs in a number of treated animals, but the

incidence of these findings was not dose-related. An inhalation LC50 of > 7.015

mg/L air was identified in this study. ToxServices identified the NOAEC at

7.015 mg/L/4h for this study based on the lack of significant systemic toxicity or

respiratory irritation observed.

CIR 2011

o Oral

In an acute oral toxicity study with limited details, male and female rats (number

and strain not stated) were exposed orally to caprylyl glycol (purity not reported).

Signs of toxicity were seen at doses ≥ 464 mg/kg and theses included sedation

and ataxia. Loss of muscle tone and dyspnea were observed specifically at a dose

of 1,000 mg/kg, and lateral position, coma, and death were observed at a dose of

1,470 mg/kg. Deaths occurred within 2 h after administration. At necropsy, pale

parenchymal organs were observed in 3,160 and 4,640 mg/kg dose groups.

Surviving animals recovered within 24 h, and study authors identified the

“nontoxic dose” of 215 mg/kg in this study, presumably based on the

neurological effects at 464 mg/kg/day described above. LD50 values of 2,240 in

males and 2,200 in females were reported. ToxServices was not able to establish

the LOAEL for systemic toxicity as the full set of doses tested and the systemic

i.e. non-neurological) effects were not reported.

Based on above data, acute exposure to caprylyl glycol via the oral route is shown to cause

reversible clinical signs of toxicity such as hunched posture, which are not considered to be

sufficient to support classification for systemic toxicity. Neurological signs were considered in

the neurotoxicity section below. No systemic toxicity was observed in one oral study while death

was reported at the dose of 1,470 mg/kg in the other oral study. However, insufficient data were

reported for this study regarding the cause of death, pathological changes in animals that died, or

effects on body weight and clinical signs other than those relevant to neurotoxicity. Therefore,

ToxServices assigned a score of Data Gap for this endpoint.

Group II* Score (repeated dose) (H, M, or L): L

Caprylyl glycol was assigned a score of Low for systemic toxicity (repeated dose) based on an oral

LOAEL of 1,000 mg/kg/day established in 28-days studies. GreenScreen® criteria classify chemicals

as a Low hazard for systemic toxicity (repeated dose) when animal studies identify oral LOAEL

values greater than 100 mg/kg/day for studies lasting at least 90 days, and when they are not

classified to GHS (CPA 2012b). Confidence in the score is high because it is based on experimental

data from a well conducted study.




ECHA 2015a and CIR 2011

o Oral

Caprylyl Glycol: In a GLP-compliant repeated dose toxicity study conducted

according to OECD 407 guideline, Wistar rats (5/sex/dose) were administered

daily doses of caprylyl glycol (purity not reported) solution in polyethylene

glycol 300 by oral gavage at doses of 0, 50, 300, or 1,000 mg/kg/day for 28 days.

The animals were evaluated for clinical signs of toxicity, body weight, food

consumption, hematology, clinical chemistry, gross pathology, and





histopathology. Neurobehavioral examination was also performed on the treated

rats which included FOB (functional observation battery), sensory evaluation,

grip strength and motor activity. No mortalities or treatment-related effects on

clinical signs of toxicity, body weight, or food consumption were noted.

Similarly, there were no treatment-related effects on hematology and clinical

chemistry parameters. Absolute and relative kidney weights were increased in

males and females at the highest dose (1,000 mg/kg/day). Also, absolute and

relative liver weights were increased only in males at 1,000 mg/kg/day. However

there were no histopathological findings in these organs. Hyperkeratosis and

epithelial hyperplasia in the pars non-glandularis of the stomach were observed in

one animal at 300 mg/kg/day and a number of animals at 1,000 mg/kg/day.

Neurobehavioral examination showed slightly reduced locomotor activity in

males and females at 1,000 mg/kg/day. Based on the microscopic findings

indicative of local irritation in one animal at 300 mg/kg/day, the study authors

identified a "No Observed Effect Level" (NOEL) of 50 mg/kg/day. In view of

only one animal being affected at 300 mg/kg/day and the absence of analogous

structures in humans, the "No Observed Adverse Effect Level" (NOAEL) of 300

mg/kg/day was established for systemic toxicity. This was based on slightly

reduced locomotor activity, elevated kidney weights and microscopic findings at

1,000 mg/kg/day. The LOAEL of 1,000 mg/kg/day is above the tripled GHS

guidance value of 300mg/kg/day for 28-day studies (guidance values tripled due

to 28-day duration of study).

Surrogate: Butane-1,2-diol: In the previously described combined repeated dose

toxicity study with reproduction/developmental toxicity screening test conducted

similar to OECD Guideline 421, Sprague-Dawley rats (10/sex/dose group) were

administered butane-1,2-diol (purity not reported) in water by oral gavage at

doses of 0, 40, 200, or 1,000 mg/kg/day. Male rats were exposed for 42 days.

Reproductive phase females were dosed for two weeks prior to mating, through

pregnancy, and then to postnatal day 3 (total of 45 days). The parental animals

were evaluated for clinical signs of toxicity, body weight, food consumption,

testes and epididymis weights, ovaries weight, gross pathology, and

histopathology. Hematology and blood serum chemistry were only evaluated in

parental males. No mortalities or treatment related effects were observed. No

gross pathological changes were observed with treatment. Slowed respiration and

decreased locomotor activity were observed in parental females at 1,000

mg/kg/day. But these effects were all transient and mild in severity and only seen

in the first week of treatment. Based on this, the study authors identified a

systemic toxicity NOEL of 200 and 1,000 mg/kg/day in female and male rats,

respectively. The LOEL of 1,000 mg/kg/day is above the doubled GHS guidance

value of 200 mg/kg/day for ~45-day studies (guidance values tripled due to 42-

45-day duration of study).

Surrogate: Decane-1,2-diol: In a GLP-compliant repeated dose toxicity study

conducted according to OECD 407, Wistar rats (5/sex/dose) were administered

daily doses of decane-1,2-diol (purity not reported) solution of ethanol and water

by oral gavage at doses of 0, 100, 300, or 1,000 mg/kg/day for 28 days. Another

two groups of rats (5/sex/dose) were administered decane-1,2-diol at doses of 0 or

1,000 mg/kg/day for 28 days and were monitored for additional 14 days. The

animals were evaluated for clinical signs of toxicity, body weight, food





consumption, hematology, clinical chemistry, urinalysis, gross pathology, and


rats which included FOB, sensory evaluation, grip strength and motor activity.

No mortalities or treatment-related effects on clinical signs of toxicity or body

weight were noted. Similarly, there were no treatment-related effects on

hematology, clinical chemistry and urinalysis parameters. High dose females

showed reduced food consumption through the treatment period but this was

similar to the controls by the end of the 14 day recovery period. On

histopathological examination, a dose-related increase in incidence and severity

of squamous epthelial hyperplasia in the forestomach was seen in males and

females at 300 and 1,000 mg/kg/day. Ulceration and increased incidence and

severity of inflammatory cell infiltrates in the forestomach were only observed in

treated animals at high dose. After a 14-day recovery period, squamous epithelial

hyperplasia remained in the animals previously dosed with 1,000 mg/kg/day, but

the severity and incidence of this finding after the treatment period were largely

reduced. Neurobehavioral examination showed reduced locomotor activity in

females and males at 1,000 mg/kg/day. Based on histological findings in the

forestomach, the study authors identified a NOEL of 100 mg/kg/day. However,

study authors stated that the findings in the forestomach may be regarded as signs

of local irritation, with analogous structures to those affected in the stomach not

existing in humans, and squamous hyperplasia of rodent forestomach and/or

limiting ridge is a common observation in gavage studies. Therefore, the

NOAEL of 300 mg/kg/day was established for systemic toxicity. This was based

on reduced locomotor activity and food consumption and microscopic findings at

1,000 mg/kg/day. The LOAEL of 1,000 mg/kg/day is above the tripled GHS

guidance value of 300 mg/kg/day for 28-day studies (guidance values tripled due

to 28-day duration of study). Based on the above data, the lowest identified oral LOAEL was 1,000 mg/kg/day established in

28-day rat studies with caprylyl glycol and its surrogate, decane-1,2-diol. This LOAEL was

based mainly on neurobehavioral effects, which were excluded from this section and considered

in the repeated dose neurotoxicity section below. Other critical effects observed at 1,000 mg/kg

included increased kidney weights, reduced food consumption and microscopic findings in the

forestomach indicative of local irritation. The lowest LOEL identified from the above studies

was 300 mg/kg/day based on the microscopic findings in the forestomach. These findings

(irritation on the pars non-glandularis and limiting ridge of the stomach) were considered to be

irrelevant to the evaluation of the toxicological hazard to human health as analogous structures to

those affected in the stomach do not exist in humans, and squamous hyperplasia of rodent

forestomach and/or limiting ridge finding is a common observation in gavage studies and

indicates local irritation rather than a systemic effect. Therefore, ToxServices relied on the

LOAEL of 1,000 mg/kg/day for systemic toxicity as the basis to assign a score of Low.

Neurotoxicity (N)

Group II Score (single dose) (vH, H, M, or L): M Caprylyl glycol was assigned a score of Moderate for neurotoxicity (single dose) based on

ToxServices classifying it to GHS Category 3 for transient narcotic effects. GreenScreen® criteria

classify chemicals as a Moderate hazard for neurotoxicity (single dose) when they are classified to

GHS category 3 (CPA 2012b). Confidence in the score is high because it is based on experimental

data from well conducted studies.







ECHA 2015b

o Oral

In the previously described acute toxicity study conducted according to OECD

401, 5 Sprague-Dawley rats (5/sex/dose) were administered caprylyl glycol

(purity not specified) in arachis oil BP at a single dose of 2,000 mg/kg by oral

gavage followed by a 14-day observation period. Clinical signs of neurotoxicity

such as lethargy and ataxia were seen in all animals at the day of dosing. By two

days after dosing (Day 2) all animals were entirely free from these signs. An oral

LD50 of greater than 2,000 mg/kg was identified in this study.

CIR 2011

o Oral

In the previously described acute oral toxicity study with limited details, male and

female rats (number and strain not stated) were exposed orally to caprylyl glycol

(purity not reported). Clinical signs of neurotoxicity were seen at doses ≥ 464

mg/kg and theses included sedation and ataxia. Loss of muscle tone and dyspnea

were observed specifically at a dose of 1,000 mg/kg, and lateral position, coma,

and death were observed at a dose of 1,470 mg/kg. Deaths occurred within 2 h

after administration. Surviving animals recovered within 24 h. LD50 values of

2,240 in males and 2,200 in females were reported.

Based on above data, acute exposure to caprylyl glycol via the oral route showed to cause

reversible clinical signs of neurotoxicity such as ataxia and lethargy. These observations are

consistent with transient narcotic effects that warrant a GHS category 3 classification.

Group II* Score (repeated dose) (H, M, or L): L Caprylyl glycol was assigned a score of Low for neurotoxicity (repeated dose) based on experimental

data. GreenScreen® criteria classify chemicals as a Low hazard for neurotoxicity (repeated dose)

when they are not classified under GHS (CPA 2012b). Confidence in the score is high because it is

based on experimental data from well conducted studies.




ECHA 2015b

o Oral

In the previously described GLP-compliant repeated dose toxicity study

conducted according to OECD 407, Wistar rats (5/sex/dose) were administered

daily doses of caprylyl glycol (purity not reported) solution in polyethylene

glycol 300 by oral gavage at doses of 0, 50, 300, or 1,000 mg/kg/day for 28 days.

The animals were evaluated for clinical signs of toxicity, body weight, food

consumption, hematology, clinical chemistry, gross pathology, and


rats which included FOB (functional observation battery), sensory evaluation,

grip strength and motor activity. Decreased locomotor activity was seen in males

and females at 1,000 mg/kg/day. Based on this ToxServices identified the

neurotoxicity NOAEL at 300 mg/kg/day. The LOAEL of 1,000 mg/kg/day is

above the tripled GHS guidance value of 300mg/kg/day for 28-day studies





(guidance values tripled due to 28-day duration of study).

Surrogate: Butane-1,2-diol: In the previously described combined repeated dose

toxicity study with reproduction/developmental toxicity screening test conducted

similar to OECD Guideline 421, Sprague-Dawley rats (10/sex/dose group) were

administered butane-1,2-diol (purity not reported) in water by oral gavage at

doses of 0, 40, 200, or 1,000 mg/kg/day. Male rats were exposed for 42 days.

Reproductive phase females were dosed for two weeks prior to mating, through

pregnancy, and then to postnatal day 3 (total of 45 days). The parental animals

were evaluated for clinical signs of toxicity, body weight, food consumption,

testes and epididymis weights, ovaries weight, gross pathology, and

histopathology. Hematology and blood serum chemistry were only evaluated in

parental males. Slowed respiration and decreased locomotor activity were

observed in parental females at 1,000 mg/kg/day. But these effects were all

transient and mild in degree and only seen in the first week of treatment. Based

on this, ToxServices identified the neurotoxicity NOEL of 200 and 1,000

mg/kg/day in female and male rats, respectively. The LOEL in females is

therefore 1,000 mg/kg/day. The LOEL of 1,000 mg/kg/day is above the doubled

GHS guidance value of 200 mg/kg/day for ~45-day studies.

Surrogate: Decane-1,2-diol: In the previously described GLP-compliant

repeated dose toxicity study conducted according to OECD 407, Wistar rats

(5/sex/dose) were administered daily doses of decane-1,2-diol (purity not

reported) solution of ethanol and water by oral gavage at doses of 0, 100, 300, or

1,000 mg/kg/day for 28 days. Another two groups of rats (5/sex/dose) were

administered decane-1,2-diol at doses of 0, or 1,000 mg/kg/day for 28 days and

were monitored for additional 14 days. The animals were evaluated for clinical

signs of toxicity, body weight, food consumption, hematology, clinical chemistry,

urinalysis, gross pathology, and histopathology. Neurobehavioral examination

was also performed on the treated rats which included FOB, sensory evaluation,

grip strength, and motor activity. Decreased locomotor activity was seen in

females and males at 1,000 mg/kg/day. Based on this, ToxServices identified the

neurotoxicity NOAEL of 300 mg/kg/day. The LOAEL of 1,000 mg/kg/day is

above the tripled GHS guidance value of 300 mg/kg/day for 28-day studies. Based on above data, repeated exposure to caprylyl glycol and its surrogates caused inhibitive

effects on the central nervous system via the oral route, mainly impairing locomotor activity.

The lowest identified oral neurotoxicity LOAEL was 1,000 mg/kg/day established in 28-day rat

studies with caprylyl glycol and its surrogate, decane-1,2-diol. This LOAEL exceeded the GHS

guidance values as explained above, and furthermore effects are likely to be indicative of the

transient narcotic effects described under neurotoxicity-single dose. Therefore caprylyl glycol is

not classifiable under GHS. In addition, effects are consistent with acute narcotic effects, which

are described under neurotoxicity (single dose).

Skin Sensitization (SnS) Group II* Score (H, M, or L): L

Caprylyl glycol was assigned a score of Low for skin sensitization based on negative findings in skin

sensitization studies. GreenScreen® criteria classify chemicals as a Low hazard for skin sensitization

when negative data, no structural alerts, and no GHS classification are available (CPA 2012b).

Confidence in the score is high because it is based on experimental data from well conducted studies.







ECHA 2015b

o In a GLP-compliant mouse local lymph node assay conducted according to OECD 429

guideline, female CBA mice (4/dose group) were dermally administered caprylyl glycol

(purity not specified) at 5, 10, or 25% w/w in propylene glycol:water. The mice were

administered 25 µL of the test substance to the dorsal surface of each ear for 3

consecutive days. Following the final application, the animals were sacrificed and the

lymph nodes isolated to perform the proliferation assay. The stimulation indices for the

5, 10, and 25% doses were 1.4, 1.2, and 2.0, respectively. As all of the stimulation

indices for the applied doses were less than 3, caprylyl glycol was not sensitizing to the

skin of mice in this study.

o In another GLP-compliant guinea pig maximization test, caprylyl glycol (purity not

specified) was not sensitizing in 10 male Hartley guinea pigs. Animals were topically

induced with 25 and 100% solution of caprylyl glycol in vaseline oil and challenged with

100% solution. No skin reactions were noted at the induction sites of any test group

animals at the 24 or 48 hour mark. Authors concluded that this substance is not

sensitizing by EU criteria.

o Caprylyl glycol (purity not specified) was not sensitizing in a maximization test

conducted according to OECD Guideline 406 performed with 10 female Dunkin-Hartley

guinea pigs. Animals were topically induced with 50 and 100% solution of caprylyl

glycol in vaseline oil and challenged with 6.5% solution. No skin reactions were noted at

the induction sites of any test group animals at the 24 or 48 hour mark. Authors

concluded that this substance is not sensitizing by EU criteria.

CIR 2011

o Caprylyl glycol (purity not specified) was not sensitizing in a maximization test

conducted according to OECD Guideline 406 performed with 20 guinea pigs (sex and

strain not specified). Animals were topically induced with 5% (in peanut oil) and 50%

(in petrolatum) and challenged with 50% solution in petrolatum. No furthered details

were provided.

Respiratory Sensitization (SnR) Group II* Score (H, M, or L): DG

Caprylyl glycol was assigned a score of Data Gap for respiratory sensitization based on the lack of

data identified for this endpoint.




No data were identified for this endpoint.

Skin Irritation/Corrosivity (IrS) Group II Score (vH, H, M, or L): L

Caprylyl glycol was assigned a score of Low for skin irritation/corrosivity based on negative findings

in animal skin irritation studies. GreenScreen® criteria classify chemicals as a Low hazard for skin

irritation/corrosivity when negative data, no structural alerts, and no GHS classification are available

(CPA 2012b). Confidence in the score is high because it is based on negative results in several

dermal irritation studies.




ECHA 2015b





o In a GLP-compliant dermal irritation test, three male New Zealand White rabbits were

administered dermal applications of 0.5 mL undiluted caprylyl glycol (purity not

specified) to clipped skin under occlusive dressing for 24 hours. Reactions were scored at

24, 48, and 72 hours after removal of the dressing. All scores for edema and erythema

were zero at all time points. Based on the results of this study, caprylyl glycol is

considered to be not irritating to the rabbit skin.

o In another GLP-compliant dermal irritation test conducted according to EU Method B.4,

three male New Zealand White rabbits were administered dermal applications of 0.5 mL

undiluted caprylyl glycol (purity not specified) to clipped skin under occlusive dressing

for 4 hours. Reactions were scored at 24, 48, and 72 hours after removal of the dressing.

The mean erythema score at 24, 48, and 72h was 0.6/4 with effects being fully reversible

within 48 hours. The mean edema score was 0. The study authors concluded that

caprylyl glycol was not irritating to the skin in this study.

o In a GLP-compliant 14-day repeated dose dermal toxicity study, Dunkin-Hartley guinea

pig (3/sex/dose) were administered daily caprylyl glycol (purity not specified) dermally at

concentrations of 6% and 3% v/v in liquid paraffin under non-occlusive conditions. An

observation period of 14 days was followed. Skin reactions (erythema and edema) were

evaluated according to Draize method immediately before each daily application and ca.

24 hours after the final application. In addition clinical signs of toxicity were recorded

daily and bodyweights weekly. Treatment sites were re-shaved at appropriate intervals

during the study. All scores for edema and erythema were zero at every time point.

Based on the results of this study, caprylyl glycol is considered to be not irritating to the

rabbit skin.

o In a GLP-compliant dermal irritation test, six New Zealand White rabbits (sex not

specified) were administered dermal applications of 0.5 mL of a 10% formulation of

caprylyl glycol (purity not specified) in vaseline oil to shaved skin under semi-occlusive

dressing for 24 hours. Reactions were scored at 24 and 72 hours after removal of the

dressing. Very slight erythema (Grade 1, barely perceptible) was noted in 1 of 6 animals

at 10% concentration. This finding had fully reversed (Grade 0) by 72 hours post

treatment. The scores for edema were zero at every time point and the primary dermal

irritation index (PDII) was 0.08/8. Based on this, caprylyl glycol is considered to be not

irritating to the rabbit skin.

Eye Irritation/Corrosivity (IrE) Group II Score (vH, H, M, or L): H

Caprylyl glycol was assigned a score of High for eye irritation/corrosivity based on experimental

data and on being associated with EU hazard statement of H319 (non-harmonized classification).

GreenScreen® criteria classify chemicals as a High hazard for eye irritation/corrosivity when they are

classified to GHS category 2A and when they are associated with EU hazard statement of H319

(CPA 2012b). Confidence in the score is high because it is based on experimental data from ocular

irritation studies with support from a non-harmonized classification.




ECHA 2015b

o In a GLP-compliant ocular irritation test conducted according to EU Method B.5, two

male New Zealand White rabbits were administered ocular instillations of 0.1 mL of

undiluted caprylyl glycol (purity not specified). The eyes were scored at 48, 72, and 96

hours after instillation and the animals were observed for 16 days. The eyes were rinsed





with deionized water at 1 hour after application due to the conjunctival redness and

chemosis which were grade 1 and 2, respectively. The mean corneal score was 1.5/4 with

the effects being fully reversible within 16 days; the mean iris score was 1/2 with the

effects being fully reversible within 9 days; the mean conjunctival score was 1/3 with the

effects being fully reversible within 11 days; and the mean chemosis score was 0.5/4 with

effects being fully reversible within 7 days. Based on this, the study authors considered

caprylyl glycol as irritating to the rabbit eye and is classified to CLP/GHS category 2A.

o An ocular irritation test followed the basic principles of the OECD guideline was

performed with six New Zealand White rabbits (3/sex) administered ocular instillations of

0.1 g undiluted caprylyl glycol (purity not specified). The animals were evaluated at 1,

24, 48 and 72 hours and 7 days after instillation of the doses. The mean corneal and iris

score was 0; the mean conjunctival score was 0.17/3 with the effects being fully reversible

within 72 hours; and the mean chemosis score was 0.67/4 with effects being fully

reversible within 72 hours. Based on this, the study authors considered caprylyl glycol as

not irritating to the rabbit eye.

o In another GLP-compliant ocular irritation study following the basic principles of the

OECD guideline, three male New Zealand White rabbits were administered ocular

instillations of 0.1 mL of a 10% formulation of caprylyl glycol (purity not specified) in

vaseline oil. The eyes were left unwashed after the application and animals were

evaluated at 1, 24, 48 and 72 hours and 4 and 5 days after instillation of the doses. The

mean corneal score was 0.3/4 with effects being fully reversible within 72 hours; the mean

conjunctival score was 1.1/3 with the effects being fully reversible within 5 days; and the

mean chemosis and iris score was 0. Based on this, the study authors considered caprylyl

glycol as not irritating to the rabbit eye. However, the study was considered inadequate

for classification purpose of neat caprylyl glycol as only a 10% test material dilution was

tested. o In another GLP-compliant ocular irritation test conducted according to OECD 405, New

Zealand White rabbits (1/dose; sex not specified) were administered ocular instillations of

0.1mL of 1%, 3%, and 5% v/v formulations of caprylyl glycol in liquid paraffin. The

animals were evaluated at t 1, 24, 48 and 72 hours after exposure. The mean scores for

conjunctivae redness, iritis, cornea opacity and conjunctivae chemosis were all < 1 at 1, 3

and 5% concentrations with effects being fully reversible within 72 hours. This indicates

that the substance is not an irritant to the rabbit eye. However, the study was considered

inadequate for classification purpose of neat caprylyl glycol as only 1, 3 and 5% test

material dilutions were tested with one animal each. ECHA 2015d

o Caprylyl glycol is self-classified by 239 notifiers as Eye Irrit. 2 with a hazard statement of

H319: causes serious eye irritation. Only 55 notifiers classified caprylyl glycol as Eye

Dam. 1 with hazard statement of H318: causes serious eye damage. CIR 2011

o In an in vitro HET-CAM assay (hen’s egg test on the chorioallantoic membrane) for

evaluating ocular irritation potential, caprylyl glycol was classified as a non-irritant at test

concentrations of 1% and 3% in neutral oil. However, a mixture of 1,2-hexanediol and

caprylyl glycol (50:50 (w/w)) was classified as a severe eye irritant when tested in the

HET-CAM assay at the concentration of 1% aqueous (effective concentration per

ingredient = 0.5%). No further details were reported.

Based on weight of evidence, a score of High was assigned. Mixed results were obtained in

experiments. Only one study that was GLP-compliant and conducted according to EU guideline





indicates that neat caprylyl glycol is irritating to the eye with effects being reversible within 16

days, meeting the GHS category 2A criteria. The second ocular irritation study on neat caprylyl

glycol, however, gave negative results. The study was not compliant with GLP. The other

available experimental studies were conducted on diluted caprylyl glycol and were considered

not sufficient for classification purpose. Therefore ToxServices used the category 2A

classification as the basis to assign a score of High.

Ecotoxicity (Ecotox)

Acute Aquatic Toxicity (AA) Score (vH, H, M, or L): H

Caprylyl glycol was assigned a score of High for acute aquatic toxicity based on its measured LC50

value of > 2.2-22 mg/L in fish. GreenScreen® criteria classify chemicals as a High hazard for acute

aquatic toxicity when acute toxicity values are between 1-10 mg/L and when they are classified to

GHS category 2 (CPA 2012b). Confidence in the score is reduced because the lowest LC50 was

reported as a range that spanned the criteria for a Moderate or High.




ECHA 2015b

o 96-hour LC50 (Brachydanio rerio, fish) >2.2 - 22 mg/L (nominal)

o 48-hour EC50 (Daphnia magna, invertebrate) 176 mg/L (nominal)

o 72-hour EC50 (Pseudokirchnerella subcapitata, green algae) 35 mg/L

Based on the above data, the lowest reported acute aquatic toxicity value for caprylyl glycol was

between 2.2 and 22 mg/L in fish, which spans the range corresponding to a score of High

according to GreenScreen® criteria.

Chronic Aquatic Toxicity (CA) Score (vH, H, M, or L): M

Caprylyl glycol was assigned a score of Moderate for chronic aquatic toxicity based on predicted

data. Confidence level was reduced due to lack of measured data. GreenScreen® criteria classify

chemicals as a Moderate hazard for chronic aquatic toxicity when chronic aquatic toxicity values are

> 1.0 to 10 mg/L (CPA 2012b). Confidence in the score is reduced because it is based on modeled

data.




ECHA 2015b

o 72 h NOEC (Pseudokirchnerella subcapitata, green algae) = 15 mg/L (growth rate).

U.S EPA 2012a

o No chronic toxicity data were identified. Caprylyl glycol was designated to neutral

organic ECOSAR chemical class. Chronic toxicity values in fish and Daphnia magna

(30-day ChV) were estimated to be between 1.0-10 mg/L, and the ChV in algae was

predicted to be 12 mg/L by ECOSAR v. 1.11 (see Appendix F).

Environmental Fate (Fate)

Persistence (P) Score (vH, H, M, L, or vL): vL

Caprylyl glycol was assigned a score of Very Low for persistence based on being readily degradable

and meeting the 10-day window in well conducted experimental tests. GreenScreen® criteria





classify chemicals that partition primarily to soil and water as a Very Low hazard for persistence

when they meet the 10-day window in ready biodegradability tests (CPA 2012b). Confidence in the

score is high because it is based on experimental biodegradation data.



o Screening: : not listed on any screening lists

ECHA 2015b

o A GLP-compliant ready biodegradability test conducted according to OECD 301 F

guideline (Manometric Respirometry Test) was performed with non-adapted activated

sludge exposed to caprylyl glycol (purity not specified) at 100 mg/L for 28 days. 11%,

61.5% and 85% degradation were achieved after 2, 9 and 28 days, respectively. These

data indicate that the 10-day window was met. The authors concluded that caprylyl

glycol was readily biodegradable in this test.

o A GLP-compliant ready biodegradability test conducted according to OECD 301 D

guideline (Closed Bottle Test) was performed with non-adapted activated sludge exposed

to caprylyl glycol (purity not specified) at 2 mg/L for 28 days. Up to 11, 66.8, 79.1 and

79.9% degradation were reached on days 7, 14, 21 and 28, respectively, indicating that

the 10-day window was met. The study authors concluded that caprylyl glycol was

readily biodegradable in this test.

o A GLP-compliant anaerobic biodegradability test conducted according to OECD 311

guideline (Measurement of Gas Production) was performed with digested sludge exposed

to caprylyl glycol (purity not specified) at 77.4 mg/L for 60 days. At the end of the

exposure period the biodegradation of the test substance reached 63 ± 3% of maximum

theoretical inorganic carbon production (ThIC). The authors concluded that caprylyl

glycol was ultimately anaerobically biodegradable in this test.

U.S. EPA 2012b

o The BIOWIN model predicted that caprylyl glycol is readily biodegradable. Using a

fugacity model, caprylyl glycol is predicted to appear mainly in the soil and water

compartments (61.3 and 36.8%, respectively), with 1.87 % in air and minor amounts in

sediment (0.07%). The predicted half-lives in soil and water are 17 days and 8 days,

respectively (See Appendix J for modeling output).

Based on the above data, caprylyl glycol meets the 10-day window in ready biodegradability tests

and was determined to be readily biodegradable. This corresponds to a GreenScreen® score of

Very Low.

Bioaccumulation (B) Score (vH, H, M, L, or vL): vL

Caprylyl glycol was assigned a score of Very Low for bioaccumulation based on its measured log

Kow and modeled BCF. GreenScreen® criteria classify chemicals as a Very Low hazard for

bioaccumulation when the BCF/BAF is ≤ 100 and when log Kow is ≤ 4 (CPA 2012b). Confidence in

the score is high because it is based on an experimental log Kow with support from a modeled BCF.




ECHA 2015b

o Caprylyl glycol has a log Kow of 2.1 as measured in a GLP-compliant OECD 117 test.

U.S. EPA 2012b

o BCFBAF predicts a BCF of 11.29 based on a measured log Kow of 2.1 (see Appendix J).





Physical Hazards (Physical)

Reactivity (Rx) Score (vH, H, M, or L): L

Caprylyl glycol was assigned a score of Low for reactivity based on ECHA’s conclusion.

Confidence level was reduced due to a lack of measured data. GreenScreen® criteria classify

chemicals as a Low hazard for reactivity when they are not explosive or self-reactive and they are not

classifiable under GHS (CPA 2012b). Confidence in the score is reduced because no experimental

data are available.




ECHA 2015b

o The explosive and oxidizing properties of caprylyl glycol were assessed by examining the

chemical structures of the test item with a list of functional groups that may indicate

oxidizing or explosive properties. Caprylyl glycol was considered not explosive or

oxidizing based on its structure and thermodynamic properties.

Flammability (F) Score (vH, H, M, or L): L Caprylyl glycol was assigned a score of Low for flammability based on its measured flash point of

140°C. GreenScreen® criteria classify chemicals as a Low hazard for flammability when they are not

classified to GHS as a flammable liquid (CPA 2012b). Confidence in the score is high because it is

based on an experimental flash point.




ECHA 2015b

o Caprylyl glycol has a flash point of 140.5°C when measured in a GLP-compliant closed

cup method conducted according to EU A.9. CIR 2011

o Caprylyl glycol is reported to have a calculated flash point of 109.1 ± 13.0°C Based on the above data, the lowest reported flash point for caprylyl glycol is 109°C, which is

greater than the cut-off value for GHS category 4 (93°C) for flammable liquids and therefore caprylyl glycol is not classified as a flammable liquid under GHS.





References

ChemIDplus. 2015. Entry for Caprylyl Glycol (CAS# 1117-86-6). United States National Library

of Medicine. Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Clean Production Action (CPA). 2012a. List Translator. Dated February 2012. Available at:

http://www.greenscreenchemicals.org/.

Clean Production Action (CPA). 2012b. The GreenScreen® for Safer Chemicals Version 1.2

Criteria. Dated: November 2012. Available at: http://www.greenscreenchemicals.org/.

Clean Production Action (CPA). 2013. The GreenScreen® for Safer Chemicals Chemical Hazard

Assessment Procedure. Version 1.2 Guidance. Dated August 31, 2013. Available at:

http://www.greenscreenchemicals.org/.

Clean Production Action (CPA). 2014. The GreenScreen® for Safer Chemicals Version 1.2

Benchmarks. Dated November 2014. Available at: http://www.greenscreenchemicals.org/.

Cosmetic Ingredient Review (CIR). 2011. CIR Expert Panel Report on the Safety Assessment of

1,2-Glycols as Used in Cosmetics. Washington, D.C.: Cosmetic Ingredient Review. Available at:

http://www.alegesanatos.ro/dbimg/files/1,2-Glycols.pdf.

Cosmetic Ingredient Review (CIR). 2012. Safety assessment of 1,2-glycols as used in cosmetics.

International Journal of Toxicology. 31(S2):147S-168S.

Cosmetic Ingredient Review (CIR). 2014. Caprylyl glycol. CIR Compendium.

European Chemicals Agency (ECHA). 2015a. Read-Across Assessment Framework (RAAF).

Available: http://echa.europa.eu/documents/10162/13628/raaf_en.pdf.

European Chemicals Agency (ECHA). 2015b. REACH Dossier for Caprylyl Glycol (CAS# 1117-

86-6).. Available at: http://apps.echa.europa.eu/registered/data/dossiers/DISS-dcebd87a-9064-427d-

e044-00144f67d031/AGGR-c5db8b0e-31f8-4385-b9c9-ea6b9b289551_DISS-dcebd87a-9064-427d-

e044-00144f67d031.html#AGGR-c5db8b0e-31f8-4385-b9c9-ea6b9b289551.

European Chemicals Agency (ECHA). 2015c. REACH Dossier for Propylene Glycol (CAS# 57-55-

6). Available at: http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d9b1d87-f99a-6f9b-

e044-00144f67d249/DISS-9d9b1d87-f99a-6f9b-e044-00144f67d249_DISS-9d9b1d87-f99a-6f9b-

e044-00144f67d249.html.

European Chemicals Agency (ECHA). 2015d. REACH Dossier for Caprylyl Glycol (CAS# 1117-

86-8). Available at: https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-

/discli/details/99610

European Union (EU). 2009. Regulation (EC) No. 1223/2009 of the European Parliament and of the

Council of 30 November 2009 on cosmetic products. Recast. Official Journal of the European Union.

L342/39. Dated December 22, 2009.


http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

http://www.greenscreenchemicals.org/




http://www.alegesanatos.ro/dbimg/files/1,2-Glycols.pdf

http://echa.europa.eu/documents/10162/13628/raaf_en.pdf

http://apps.echa.europa.eu/registered/data/dossiers/DISS-dcebd87a-9064-427d-e044-00144f67d031/AGGR-c5db8b0e-31f8-4385-b9c9-ea6b9b289551_DISS-dcebd87a-9064-427d-e044-00144f67d031.html#AGGR-c5db8b0e-31f8-4385-b9c9-ea6b9b289551



http://apps.echa.europa.eu/registered/data/dossiers/DISS-9d9b1d87-f99a-6f9b-e044-00144f67d249/DISS-9d9b1d87-f99a-6f9b-e044-00144f67d249_DISS-9d9b1d87-f99a-6f9b-e044-00144f67d249.html



https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/99610

https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/99610




Godfrey, D. 2012. Preservation of Moisturizers. Chapter 23 in Treatment of Dry Skin Syndrome.

Ed. M. Loden and H.I. Maibach. Berlin Heidelberg: Springer-Verlag. 355-366.

Lawan, K., M. Kanlayavattanakul, and N. Lourith. 2009. Antimicrobial efficacy of caprylyl glycol

and ethylhexylglycerine in emulsion. Journal of Health Research. 23(1):1-3.

Organisation for Economic Co-operation and Development (OECD). 2014. Guidance on Grouping

of Chemicals, Second Edition. Series on Testing and Assessment No. 194. Available:

http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2014)4&docl

anguage=en.

Papageorgiou, S., A. Varvaresou, E. Tsirivas, and C. Demetzos. 2010. New alternatives to

cosmetics preservation. Journal of Cosmetic Science. 61:107-123.

Pharos. 2015. Pharos Chemical and Material Library Entry for Caprylyl glycol (CAS# 1117-86-6).

Available at: http://www.pharosproject.net/material.

Pillai, R., G. Schmaus, A. Pfeiffer, S. Lange and A. Trunet. 2008. 1,2-Alkanediols for cosmetic

preservation. Cosmetics and Toiletries. 123(10):53.

Toxtree. 2014. Estimation of Toxic Hazard- A Decision Tree Approach v2.6.6. Available at:

http://toxtree.sourceforge.net.

ToxServices. 2013. SOP 1.69: GreenScreen® Hazard Assessments. Dated: August 17, 2013.

UNEP OECD Screening Information Datasets (SIDS). 2001. SIDS Initial Assessment Profile for

Propylene Glycol (CAS# 57-55-6). Available: http://www.inchem.org/documents/sids/sids/57-55-

6.pdf

United States Department of Transportation (U.S. DOT). 2008a. Chemicals Listed with

Classification. 49 CFR § 172.101. Available at: http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-

vol2/pdf/CFR-2008-title49-vol2-sec172-101.pdf.

United States Department of Transportation (U.S. DOT). 2008b. Classification Criteria. 49 CFR §

173. Available at: http://www.ecfr.gov/cgi-bin/text-

idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl.

United States Environmental Protection Agency (U.S. EPA). 2010. The Use of Structure-Activity

Relationships (SAR) in the High Production Volume Chemicals Challenge Program.

United States Environmental Protection Agency (U.S. EPA). 2012a. ECOSAR v1.11. Washington,

DC, USA. Available at: http://www.epa.gov/oppt/newchems/tools/21ecosar.htm/.

United States Environmental Protection Agency (U.S. EPA). 2012b. Estimation Programs Interface

(EPI) SuiteTM Web, v4.11, Washington, DC, USA. Available at:

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm.


http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2014)4&doclanguage=en

http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2014)4&doclanguage=en

http://www.pharosproject.net/material

http://toxtree.sourceforge.net/

http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-vol2/pdf/CFR-2008-title49-vol2-sec172-101.pdf

http://www.gpo.gov/fdsys/pkg/CFR-2008-title49-vol2/pdf/CFR-2008-title49-vol2-sec172-101.pdf

http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl

http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&tpl=/ecfrbrowse/Title49/49cfr173_main_02.tpl

http://www.epa.gov/oppt/newchems/tools/21ecosar.htm/

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm




Varvaresou, A., S. Papageorgiou, E. Tsirivas, E. Protopapa, H. Kintziou, V. Kefala, and C.

Demetzos. 2009. Self-preserving cosmetics. International Journal of Cosmetic Science. 31:163-

175.

Virtual Models for Evaluating the Properties of Chemicals within a Global Architecture (VEGA).

2012. Predictive Model Platform. Available at: http://www.vega-qsar.eu/index.php.


http://www.vega-qsar.eu/index.php




APPENDIX A: Hazard Benchmark Acronyms

(in alphabetical order)

(AA) Acute Aquatic Toxicity

(AT) Acute Mammalian Toxicity

(B) Bioaccumulation

(C) Carcinogenicity

(CA) Chronic Aquatic Toxicity

(D) Developmental Toxicity

(E) Endocrine Activity

(F) Flammability

(IrE) Eye Irritation/Corrosivity

(IrS) Skin Irritation/Corrosivity

(M) Mutagenicity and Genotoxicity

(N) Neurotoxicity

(P) Persistence

(R) Reproductive Toxicity

(Rx) Reactivity

(SnS) Sensitization- Skin

(SnR) Sensitization- Respiratory

(ST) Systemic/Organ Toxicity



Limited license provided to EDF for posting via EDF’s website at https://www.edf.org/. Further copying, resale, and distribution are expressly prohibited. Page 28 of 39

APPENDIX B: Results of Automated GreenScreen® Score Calculation for Caprylyl Glycol (CAS# 1117-86-6)



Limited license provided to EDF for posting via EDF’s website at https://www.edf.org/. Further copying, resale, and distribution are expressly prohibited. Page 29 of 39

APPENDIX C: Pharos Output for Caprylyl Glycol (CAS# 1117-86-6)





APPENDIX D: Toxtree Carcinogenicity Results for Caprylyl Glycol (CAS# 1117-86-6)





APPENDIX E: VEGA Carcinogenicity Results for Caprylyl Glycol (CAS# 1117-86-6)













APPENDIX F: ECOSAR Modeling Results for Caprylyl Glycol (CAS# 1117-86-6)

ECOSAR Version 1.11 Results Page

SMILES: OCC(O)CCCCCC

CHEM: 1,2-OCTANEDIOL

CAS Num: 001117-86-8

ChemID1:

MOL FOR: C8 H18 O2

MOL WT: 146.23

Log Kow: 1.673 (EPISuite Kowwin v1.68 Estimate)

Log Kow: 2.100 (User Entered)

Log Kow: (PhysProp DB exp value - for comparison only)

Melt Pt: (User Entered for Wat Sol estimate)

Melt Pt: (deg C, PhysProp DB exp value for Wat Sol estimate)

Wat Sol: 1268 (mg/L, EPISuite WSKowwin v1.43 Estimate)

Wat Sol: (User Entered)

Wat Sol: (PhysProp DB exp value)

--------------------------------------

Values used to Generate ECOSAR Profile

--------------------------------------

Log Kow: 2.100 (User Entered)

Wat Sol: 1268 (mg/L, EPISuite WSKowwin v1.43 Estimate)

------------------------------------------------

Available Measured Data from ECOSAR Training Set

------------------------------------------------

No Data Available

--------------------------------------

ECOSAR v1.1 Class-specific Estimations

--------------------------------------

Neutral Organics

Predicted

ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ================== ======== ======

==========

Neutral Organics : Fish 96-hr. LC50 97.686

Neutral Organics : Daphnid 48-hr. LC50 55.981

Neutral Organics : Green Algae 96-hr. EC50 43.323

Neutral Organics : Fish ChV 9.653

Neutral Organics : Daphnid ChV 5.601

Neutral Organics : Green Algae ChV 11.581

Neutral Organics : Fish (SW) 96-hr. LC50 123.053





Neutral Organics : Mysid 96-hr. LC50 85.462

Neutral Organics : Fish (SW) ChV 14.197

Neutral Organics : Mysid (SW) ChV 7.171

Neutral Organics : Earthworm 14-day LC50 248.240

Note: * = asterisk designates: Chemical may not be soluble enough to

measure this predicted effect. If the effect level exceeds the

water solubility by 10X, typically no effects at saturation (NES)

are reported.

------------------------------

Class Specific LogKow Cut-Offs

------------------------------

If the log Kow of the chemical is greater than the endpoint specific cut-offs

presented below, then no effects at saturation are expected for those endpoints.

Neutral Organics:

----------------

Maximum LogKow: 5.0 (Fish 96-hr LC50; Daphnid LC50, Mysid LC50)

Maximum LogKow: 6.0 (Earthworm LC50)

Maximum LogKow: 6.4 (Green Algae EC50)

Maximum LogKow: 8.0 (ChV)





APPENDIX J: EPISuite Modeling Results for Caprylyl Glycol (CAS# 1117-86-6)

CAS Number: 1117-86-8

SMILES: OCC(O)CCCCCC

CHEM: 1,2-OCTANEDIOL

MOL FOR: C8 H18 O2

MOL WT: 146.23

------------------------------ EPI SUMMARY (v4.11) --------------------------

Physical Property Inputs:

Log Kow (octanol-water): 2.10

Boiling Point (deg C): ------

Melting Point (deg C): ------

Vapor Pressure (mm Hg): ------

Water Solubility (mg/L): ------

Henry LC (atm-m3/mole): ------

Log Octanol-Water Partition Coef (SRC):

Log Kow (KowWIN v1.68 estimate) = 1.67

Boiling Pt, Melting Pt, Vapor Pressure Estimations (MPBPVP v1.43):

Boiling Pt (deg C): 253.11 (Adapted Stein & Brown method)

Melting Pt (deg C): 23.77 (Mean or Weighted MP)

VP(mm Hg,25 deg C): 0.00163 (Mean VP of Antoine & Grain methods)

VP (Pa, 25 deg C): 0.217 (Mean VP of Antoine & Grain methods)

Water Solubility Estimate from Log Kow (WSKow v1.42):

Water Solubility at 25 deg C (mg/L): 1268

log Kow used: 2.10 (user entered)

no-melting pt equation used

Water Sol Estimate from Fragments:

Wat Sol (v1.01 est) = 35062 mg/L

ECOSAR Class Program (ECOSAR v1.11):

Class(es) found:

Neutral Organics

Henrys Law Constant (25 deg C) [HENRYWIN v3.20]:

Bond Method: 7.16E-007 atm-m3/mole (7.25E-002 Pa-m3/mole)

Group Method: 7.39E-010 atm-m3/mole (7.48E-005 Pa-m3/mole)

For Henry LC Comparison Purposes:

User-Entered Henry LC: not entered

Henrys LC [via VP/WSol estimate using User-Entered or Estimated values]:

HLC: 2.473E-007 atm-m3/mole (2.506E-002 Pa-m3/mole)

VP: 0.00163 mm Hg (source: MPBPVP)

WS: 1.27E+003 mg/L (source: WSKowWIN)

Log Octanol-Air Partition Coefficient (25 deg C) [KoaWIN v1.10]:

Log Kow used: 2.10 (user entered)





Log Kaw used: -4.534 (HenryWin est)

Log Koa (KoaWIN v1.10 estimate): 6.634

Log Koa (experimental database): None

Probability of Rapid Biodegradation (BIOWIN v4.10):

Biowin1 (Linear Model): 1.1038

Biowin2 (Non-Linear Model): 0.9934

Expert Survey Biodegradation Results:

Biowin3 (Ultimate Survey Model): 3.4943 (days-weeks)

Biowin4 (Primary Survey Model): 4.1647 (days)

MITI Biodegradation Probability:

Biowin5 (MITI Linear Model): 0.8456

Biowin6 (MITI Non-Linear Model): 0.9432

Anaerobic Biodegradation Probability:

Biowin7 (Anaerobic Linear Model): 0.6944

Ready Biodegradability Prediction: YES

Hydrocarbon Biodegradation (BioHCwin v1.01):

Structure incompatible with current estimation method!

Sorption to aerosols (25 Dec C)[AEROWIN v1.00]:

Vapor pressure (liquid/subcooled): 0.212 Pa (0.00159 mm Hg)

Log Koa (Koawin est): 6.634

Kp (particle/gas partition coef. (m3/µg)):

Mackay model: 1.42E-005

Octanol/air (Koa) model: 1.06E-006

Fraction sorbed to airborne particulates (phi):

Junge-Pankow model: 0.000511

Mackay model: 0.00113

Octanol/air (Koa) model: 8.45E-005

Atmospheric Oxidation (25 deg C) [AopWin v1.92]:

Hydroxyl Radicals Reaction:

OVERALL OH Rate Constant = 21.5418 E-12 cm3/molecule-sec

Half-Life = 0.497 Days (12-hr day; 1.5E6 OH/cm3)

Half-Life = 5.958 Hrs.

Ozone Reaction:

No Ozone Reaction Estimation

Fraction sorbed to airborne particulates (phi):

0.000821 (Junge-Pankow, Mackay avg)

8.45E-005 (Koa method)

Note: the sorbed fraction may be resistant to atmospheric oxidation

Soil Adsorption Coefficient (KocWIN v2.00):

Koc: 10 L/kg (MCI method)

Log Koc: 1.000 (MCI method)

Koc: 18.36 L/kg (Kow method)

Log Koc: 1.264 (Kow method)





Aqueous Base/Acid-Catalyzed Hydrolysis (25 deg C) [HYDROWIN v2.00]:

Rate constants can NOT be estimated for this structure!

Bioaccumulation Estimates (BCFBAF v3.01):

Log BCF from regression-based method = 1.053 (BCF = 11.29 L/kg wet-wt)

Log Biotransformation Half-life (HL) = -1.1566 days (HL = 0.06972 days)

Log BCF Arnot-Gobas method (upper trophic) = 0.921 (BCF = 8.332)

Log BAF Arnot-Gobas method (upper trophic) = 0.921 (BAF = 8.332)

log Kow used: 2.10 (user entered)

Volatilization from Water:

Henry LC: 7.16E-007 atm-m3/mole (estimated by Bond SAR Method)

Half-Life from Model River: 990.1 hours (41.25 days)

Half-Life from Model Lake: 1.09E+004 hours (454.3 days)

Removal in Wastewater Treatment:

Total removal: 2.39 percent

Total biodegradation: 0.10 percent

Total sludge adsorption: 2.25 percent

Total to Air: 0.04 percent

(using 10000 hr. Bio P,A,S)

Level III Fugacity Model:

Mass Amount Half-Life Emissions

(percent) (hr.) (kg/hr.)

Air 1.87 11.9 1000

Water 36.8 208 1000

Soil 61.3 416 1000

Sediment 0.0775 1.87e+003 0

Persistence Time: 257 hr.





Licensed GreenScreen® Profilers

Caprylyl Glycol GreenScreen® Evaluation Prepared by:

Mouna Zachary, Ph.D.

Toxicologist

ToxServices LLC

Caprylyl Glycol GreenScreen® Evaluation QC’d by:

Bingxuan Wang, Ph.D.

Toxicologist

ToxServices LLC


Date post:	07-Mar-2018
Category:	Documents
Upload:	hoangkien
View:	216 times
Download:	2 times

Caprylyl Glycol (CAS #1117-86-6) GreenScreen for Safer...

Documents